TLK2

Summary

TLK2 (tousled like kinase 2, HGNC:11842) is a protein-coding gene on chromosome 17q23.2, encoding Serine/threonine-protein kinase tousled-like 2 (Q86UE8). Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation. In precision oncology, TLK2 Amplification confers sensitivity to Go6983 + GF109203X in Breast Cancer (CIViC Level D). It is a selective cancer dependency (DepMap: 62.5% of cell lines).

This gene encodes a nuclear serine/threonine kinase that was first identified in Arabidopsis. The encoded protein is thought to function in the regulation of chromatin assembly in the S phase of the cell cycle by regulating the levels of a histone H3/H4 chaperone. This protein is associated with double-strand break repair of DNA damage caused by radiation. Pseudogenes of this gene are present on chromosomes 10 and 17. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 11011 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 321 total — 42 pathogenic, 41 likely-pathogenic (top 10% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 4 regions constrained (≈73% of expected missense variation)
• GTEx eGene: eQTL in 10 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 53
• ChEMBL bioactivity: 11 clinical-phase molecules tested; no curated mechanism-of-action drug
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer dependency (DepMap): dependent in 62.5% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.10 (highly constrained)
• MANE Select transcript: NM_006852

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11842
Approved symbol	TLK2
Name	tousled like kinase 2
Location	17q23.2
Locus type	gene with protein product
Status	Approved
Aliases	PKU-ALPHA, MGC44450
Ensembl gene	ENSG00000146872
Ensembl biotype	protein_coding
OMIM	608439
Entrez	11011

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 53 protein_coding, 9 retained_intron, 7 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000346027

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 1, TSL 3: 1, TSL 4: 4, TSL 5: 6

ENST00000346027, ENST00000326270, ENST00000343388, ENST00000577616, ENST00000578931, ENST00000579450, ENST00000580203, ENST00000580705, ENST00000581041, ENST00000581286, ENST00000582195, ENST00000582660, ENST00000582809, ENST00000583310, ENST00000583690, ENST00000583843, ENST00000584367, ENST00000682075, ENST00000682085, ENST00000682149, ENST00000682203, ENST00000682274, ENST00000682827, ENST00000683104, ENST00000683536, ENST00000683737, ENST00000684012, ENST00000684133, ENST00000684213, ENST00000684440, ENST00000684553, ENST00000684772, ENST00000902349, ENST00000902350, ENST00000902351, ENST00000902352, ENST00000902353, ENST00000902354, ENST00000902355, ENST00000931871, ENST00000931872, ENST00000931873, ENST00000931874, ENST00000931875, ENST00000931876, ENST00000931877, ENST00000931878, ENST00000931879, ENST00000931880, ENST00000963455, ENST00000963456, ENST00000963457, ENST00000963458, ENST00000963459, ENST00000963460, ENST00000963461, ENST00000963462, ENST00000963463, ENST00000963464, ENST00000963465, ENST00000963466, ENST00000963467, ENST00000963468, ENST00000963469, ENST00000986361, ENST00001014800, ENST00001014801, ENST00001014803, ENST00001115484, ENST00001130967, ENST00001143587

RefSeq mRNA: 13 — MANE Select: NM_006852 NM_001284333, NM_001284363, NM_001330418, NM_001375269, NM_001375270, NM_001375271, NM_001375272, NM_001375273, NM_001411074, NM_001438203, NM_001438204, NM_001438205, NM_006852

CCDS: CCDS11633, CCDS45753, CCDS62283, CCDS82182, CCDS92374

Canonical transcript exons

ENST00000346027 — 22 exons

Exon	Start	End
ENSE00001181136	62586135	62586226
ENSE00001181139	62580111	62580192
ENSE00001181142	62578477	62578574
ENSE00001181144	62576709	62576775
ENSE00001181147	62573215	62573367
ENSE00001181150	62565001	62565137
ENSE00001635332	62481121	62481206
ENSE00002458635	62552302	62552397
ENSE00002472645	62600651	62600820
ENSE00002527627	62560016	62560126
ENSE00002530141	62553663	62553755
ENSE00003473758	62520773	62520844
ENSE00003503571	62536170	62536337
ENSE00003505997	62524236	62524331
ENSE00003619493	62596585	62596674
ENSE00003663845	62608041	62608148
ENSE00003670766	62602042	62602180
ENSE00003679960	62522204	62522273
ENSE00003786926	62523134	62523177
ENSE00003789599	62606130	62606241
ENSE00003903915	62478825	62479290
ENSE00004803234	62612392	62615481

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 97.26.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3497 / max 14.3536, expressed in 154 samples.

Highest expression (Bgee): calcaneal tendon, sural nerve, colonic epithelium, bone marrow cell, ventricular zone.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TLK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

10 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	7.7e-06	-0.15	17:62634812:T:C
Skin Sun Exposed Lower leg	eqtl	5.0e-03	+0.10	17:62479320:A:G
Skin Not Sun Exposed Suprapubic	eqtl	8.6e-03	+0.15	17:63365469:T:C
Brain Spinal cord cervical c-1	eqtl	9.0e-03	+0.69	17:62047208:T:A
Cells Cultured fibroblasts	eqtl	9.8e-03	+0.31	17:62529033:C:T
Heart Left Ventricle	eqtl	1.9e-02	+0.36	17:62495864:A:G
Brain Anterior cingulate cortex BA24	eqtl	2.4e-02	+1.01	17:61563365:T:C
Colon Sigmoid	eqtl	2.7e-02	-0.55	17:62776362:T:C
Muscle Skeletal	eqtl	3.5e-02	-0.07	17:62149643:A:C
Nerve Tibial	eqtl	3.6e-02	-0.10	17:62663603:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
208301	0.3082	127
162111	0.0416	24

Top tissues by expression

showing 100 of 256 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.26	gold quality
sural nerve	UBERON:0015488	96.68	gold quality
colonic epithelium	UBERON:0000397	95.38	gold quality
bone marrow cell	CL:0002092	95.08	gold quality
ventricular zone	UBERON:0003053	94.79	gold quality
adrenal tissue	UBERON:0018303	94.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.89	gold quality
ganglionic eminence	UBERON:0004023	93.76	gold quality
left testis	UBERON:0004533	93.30	gold quality
endometrium epithelium	UBERON:0004811	93.18	gold quality
right testis	UBERON:0004534	92.95	gold quality
cortical plate	UBERON:0005343	92.87	gold quality
stromal cell of endometrium	CL:0002255	92.09	gold quality
testis	UBERON:0000473	91.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.97	gold quality
gastrocnemius	UBERON:0001388	89.92	gold quality
muscle of leg	UBERON:0001383	89.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.73	gold quality
islet of Langerhans	UBERON:0000006	88.98	gold quality
popliteal artery	UBERON:0002250	88.50	gold quality
tibial artery	UBERON:0007610	88.49	gold quality
granulocyte	CL:0000094	87.89	gold quality
tibial nerve	UBERON:0001323	87.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.66	gold quality
smooth muscle tissue	UBERON:0001135	87.62	gold quality
leukocyte	CL:0000738	87.60	gold quality
monocyte	CL:0000576	87.47	gold quality
body of uterus	UBERON:0009853	87.34	gold quality
skin of leg	UBERON:0001511	87.30	gold quality
aorta	UBERON:0000947	87.27	gold quality
right lung	UBERON:0002167	87.27	gold quality
ectocervix	UBERON:0012249	87.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.17	gold quality
lower esophagus	UBERON:0013473	87.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.08	gold quality
right coronary artery	UBERON:0001625	87.04	gold quality
prefrontal cortex	UBERON:0000451	87.00	gold quality
skin of abdomen	UBERON:0001416	87.00	gold quality
left ovary	UBERON:0002119	86.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.88	gold quality
rectum	UBERON:0001052	86.86	gold quality
mucosa of transverse colon	UBERON:0004991	86.70	gold quality
upper lobe of left lung	UBERON:0008952	86.64	gold quality
mucosa of stomach	UBERON:0001199	86.59	gold quality
lower esophagus mucosa	UBERON:0035834	86.55	gold quality
vermiform appendix	UBERON:0001154	86.23	gold quality
right ovary	UBERON:0002118	86.23	gold quality
left coronary artery	UBERON:0001626	86.20	gold quality
ascending aorta	UBERON:0001496	86.12	gold quality
endocervix	UBERON:0000458	86.10	gold quality
thoracic aorta	UBERON:0001515	86.10	gold quality
descending thoracic aorta	UBERON:0002345	86.04	gold quality
esophagus	UBERON:0001043	85.82	gold quality
transverse colon	UBERON:0001157	85.61	gold quality
cerebellar hemisphere	UBERON:0002245	85.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.53	gold quality
cerebellar cortex	UBERON:0002129	85.52	gold quality
gall bladder	UBERON:0002110	85.38	gold quality
metanephric glomerulus	UBERON:0004736	85.38	gold quality
left uterine tube	UBERON:0001303	85.33	gold quality
omental fat pad	UBERON:0010414	85.33	gold quality
right atrium auricular region	UBERON:0006631	85.26	gold quality
peritoneum	UBERON:0002358	85.24	gold quality
minor salivary gland	UBERON:0001830	85.17	gold quality
left lobe of thyroid gland	UBERON:0001120	85.11	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.03	gold quality
right lobe of thyroid gland	UBERON:0001119	84.99	gold quality
tendon	UBERON:0000043	84.96	gold quality
adenohypophysis	UBERON:0002196	84.89	gold quality
right adrenal gland cortex	UBERON:0035827	84.83	gold quality
vagina	UBERON:0000996	84.78	gold quality
thyroid gland	UBERON:0002046	84.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.73	gold quality
left adrenal gland	UBERON:0001234	84.68	gold quality
left adrenal gland cortex	UBERON:0035825	84.67	gold quality
spinal cord	UBERON:0002240	84.63	gold quality
pancreas	UBERON:0001264	84.57	gold quality
esophagus mucosa	UBERON:0002469	84.57	gold quality
right adrenal gland	UBERON:0001233	84.51	gold quality
uterine cervix	UBERON:0000002	84.49	gold quality
coronary artery	UBERON:0001621	84.42	gold quality
right frontal lobe	UBERON:0002810	84.37	gold quality
upper lobe of lung	UBERON:0008948	84.18	gold quality
adrenal gland	UBERON:0002369	84.12	gold quality
body of stomach	UBERON:0001161	84.07	gold quality
anterior cingulate cortex	UBERON:0009835	84.05	gold quality
cerebellum	UBERON:0002037	84.00	gold quality
ovary	UBERON:0000992	83.96	gold quality
stomach	UBERON:0000945	83.91	gold quality
body of pancreas	UBERON:0001150	83.82	gold quality
spleen	UBERON:0002106	83.76	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.74	gold quality
apex of heart	UBERON:0002098	83.67	gold quality
zone of skin	UBERON:0000014	83.62	gold quality
paraflocculus	UBERON:0005351	83.44	gold quality
hypothalamus	UBERON:0001898	83.30	gold quality
heart left ventricle	UBERON:0002084	83.26	gold quality
oviduct epithelium	UBERON:0004804	83.13	gold quality
cardiac atrium	UBERON:0002081	83.11	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.43

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Testis	tissue	42.2
Postcentral gyrus	tissue	32.0
Choroid plexus	tissue	31.8
Retina	tissue	29.8
Locus coeruleus	tissue	29.6
Nucleus accumbens	tissue	29.0
Cerebellum	tissue	28.2
Hippocampus	tissue	27.6
Pons	tissue	27.3
Substantia nigra	tissue	27.2
Corpus callosum	tissue	27.0
Spinal cord	tissue	26.7
Thalamus	tissue	26.5
Midbrain	tissue	26.3
Superior colliculi	tissue	26.0
Medulla oblongata	tissue	25.3
Bone marrow	tissue	25.0
Putamen	tissue	24.8
Hypothalamus	tissue	24.7
Periaqueductal gray	tissue	24.3
Septum	tissue	24.0
Skeletal muscle	tissue	23.2
Cerebral cortex	tissue	23.1
Motor cortex	tissue	23.1
Occipital cortex	tissue	22.9
Ventral forebrain	tissue	22.8
Prefrontal cortex	tissue	22.7
Hippocampal formation	tissue	22.5
Thyroid gland	tissue	22.4
Entorhinal cortex	tissue	22.4
Basal ganglia	tissue	22.2
Olfactory bulb	tissue	22.2
Somatosensory cortex	tissue	22.0
Retrosplenial cortex	tissue	21.7
Retrosplenial and cingulate cortex	tissue	21.6
Amygdala	tissue	21.4
Temporal cortex	tissue	20.9
Thymus	tissue	20.5
Insular cortex	tissue	20.5
Lymph node	tissue	19.5
Esophagus	tissue	18.0
Frontal cortex	tissue	17.8
Caudate putamen	tissue	17.8
Heart muscle	tissue	17.4
Tongue	tissue	17.4
Skin 1	tissue	17.3
Endometrium 1	tissue	16.9
Urinary bladder	tissue	16.0
Appendix	tissue	15.7
Small intestine	tissue	15.4
Gallbladder	tissue	15.3
Spleen	tissue	15.1
Duodenum	tissue	15.1
Tonsil	tissue	15.1
Colon	tissue	15.0
Ovary	tissue	14.5
Adipose tissue	tissue	14.2
Pancreas	tissue	14.0
Stomach 1	tissue	13.9
Parathyroid gland	tissue	13.8

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (42.2), Corpus callosum, genu (white matter) (41.3), Vermis (38.4), Corpus callosum, splenium (white matter) (37.3), Paraventricular nucleus (37.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TLK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 135 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.103, missense Z 6.55 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000346027 splits into 4 regions with different missense tolerance; 2 are missense-constrained (≈73% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
17:62,481,126–62,536,335	105 / 218.4	0.48	no
17:62,536,336–62,578,532	94 / 282.6	0.33	yes (p 3.3e-29)
17:62,578,533–62,612,489	81 / 370.9	0.22	yes (p 3.2e-51)
17:62,612,490–62,612,562	19 / 29.2	0.65	no
DepMap (CRISPR cell-line fitness): dependent in 62.5% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): WM1799 (-1.815), UACC-893 (-1.548), IGR-39 (-1.479), COLO-678 (-1.332), MCF-7 (-1.329), A-375 (-1.3), Du4475 (-1.262), PA-TU-8902 (-1.246), G-401 (-1.213), HUP-T3 (-1.185), Hs 852.T (-1.153), SW1463 (-1.153), KP-2 (-1.078), SNU-182 (-1.069), LOU-NH91 (-1.057).

Literature-anchored findings (GeneRIF, showing 13)

• ASF1 cellular levels are tightly controlled by distinct pathways and provide a molecular mechanism for post-translational regulation of dASF1 and hASF1a by TLK kinases. (PMID:20016786)
• TLKs appear to be intimately linked to the pattern of resistance to DNA damage, and specifically double-strand breaks. (PMID:21647934)
• TLK2 plays a role in Kaposi’s sarcoma-associated herpesvirus reactivation. (PMID:23414760)
• Tlk2 promotes Asf1A function during the DNA damage response in G2 to allow for proper restoration of chromatin structure at the break site and subsequent recovery from the arrest. (PMID:26931568)
• Results show that TLK2 overexpression correlates with increased genome-wide copy number aberrations in breast cancer cells, impairs cell-cycle checkpoint signaling in response to DNA damage. (PMID:27489360)
• TLK2 is amplified in aggressive luminal breast neoplasms (PMID:27694828)
• haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. (PMID:29861108)
• Molecular basis of TLK2 activation and inhibition has been dissected. (PMID:29955062)
• Study shows that TLK2 expression is increased in glioblastoma. Furthermore, TLK2 overexpression resulted in tumor growth and metastasis via SRC signaling pathway. (PMID:30207834)
• Tousled-Like Kinases Suppress Innate Immune Signaling Triggered by Alternative Lengthening of Telomeres. (PMID:32755577)
• Functional analysis of TLK2 variants and their proximal interactomes implicates impaired kinase activity and chromatin maintenance defects in their pathogenesis. (PMID:33323470)
• Tousled-like kinase 2 targets ASF1 histone chaperones through client mimicry. (PMID:35136069)
• [Effect of TLK2 Expression Regulated by MiR-21 on Proliferation and Apoptosis of Acute Myeloid Leukemia Cells]. (PMID:38926950)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tlk2	ENSDARG00000010779
mus_musculus	Tlk2	ENSMUSG00000020694
rattus_norvegicus	Tlk2	ENSRNOG00000006285
drosophila_melanogaster	Tlk	FBGN0283657
caenorhabditis_elegans		WBGENE00006579

Paralogs (2): TTK (ENSG00000112742), TLK1 (ENSG00000198586)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1346023) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 17 distinct phenotype terms.

Mouse phenotype (MP)	Records
anemia	1
decreased embryo size	1
abnormal embryo turning	1
decreased trophoblast giant cell number	1
abnormal placenta labyrinth morphology	1
abnormal placenta vasculature	1
abnormal bone structure	1
small placenta	1
pale placenta	1
abnormal trophoblast layer morphology	1
increased bone mineral content	1
lethality throughout fetal growth and development, complete penetrance	1
preweaning lethality, complete penetrance	1
disorganized placental labyrinth	1
abnormal syncytiotrophoblast morphology	1
prenatal lethality prior to heart atrial septation	1
decreased spongiotrophoblast cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Trypanosoma brucei brucei TREU927	Q57YS8	89.8%	Diamond
Xenopus tropicalis	Q08CW1	87.8%	Diamond
Chlamydia muridarum str. Nigg	Q9PK92	78.7%	Diamond
Arabidopsis thaliana	Q39238	51.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
METTL2A	protein-coding	339175
MRC2	protein-coding	9902
MARCHF10-DT	ncRNA	101927877
MARCHF10-AS1	ncRNA	105371855
MARCHF10	protein-coding	162333
EFCAB3	protein-coding	146779

Protein

Protein identifiers

Serine/threonine-protein kinase tousled-like 2 — Q86UE8 (reviewed: Q86UE8)

Alternative names: HsHPK, PKU-alpha, Tousled-like kinase 2

All UniProt accessions (14): Q86UE8, A0A804HIB4, A0A804HJM7, A0A804HJX3, A0A804HJZ9, A0A804HK10, A0A804HKD4, A0A804HKF1, J3KRK0, J3QLK5, J3QQN4, J3QR10, J3QS44, J3QS73

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation. Phosphorylates the chromatin assembly factors ASF1A and ASF1B. Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly. Negative regulator of amino acid starvation-induced autophagy.

Subunit / interactions. Monomer. May form homodimers; homodimerization may enhance autophosphoylation and enzymatic activity. Heterodimer with TLK1. Interacts with YWHAZ; association with 14-3-3 proteins such as YWHAZ regulates subcellular location. May also interact with FEZ1/LZTS1 and FEZ2. Interacts with CHD7 and CHD8. Interacts with DYNLL1/LC8.

Subcellular location. Nucleus. Nucleoplasm. Cytoplasm. Perinuclear region. Cytoskeleton.

Tissue specificity. Detected in placenta, fetal liver, kidney, pancreas, heart and skeletal muscle. Highly expressed in testis. Detected in spleen, thymus, colon, ovary, small intestine, prostate and peripheral blood leukocytes. Almost undetectable in liver and lung.

Post-translational modifications. Phosphorylated at Ser-750, probably by CHEK1. Autophosphorylated; phosphorylation promotes the assembly of higher order oligomers and enzymatic activity.

Disease relevance. Intellectual developmental disorder, autosomal dominant 57 (MRD57) [MIM:618050] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD57 is characterized by delayed psychomotor development apparent in infancy or early childhood, and a variety of behavioral abnormalities. Affected individuals may have severe gastro-intestinal problems, and facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Cell cycle-regulated, with maximal activity in the S-phase. Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase, probably by CHEK1, possibly at Ser-750. This inhibition is cell cycle checkpoint- and ATM-dependent.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86UE8-1	1	yes
Q86UE8-2	2
Q86UE8-3	3

RefSeq proteins (13): NP_001271262, NP_001271292, NP_001317347, NP_001362198, NP_001362199, NP_001362200, NP_001362201, NP_001362202, NP_001398003, NP_001425132, NP_001425133, NP_001425134, NP_006843* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF00069

Catalyzed reactions (Rhea)

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (99 total): sequence variant 29, strand 14, helix 13, mutagenesis site 10, modified residue 7, sequence conflict 5, region of interest 4, turn 4, compositionally biased region 3, coiled-coil region 3, binding site 2, splice variant 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
7LO0	Structure of human ASF1a in complex with a TLK2 peptide	X-RAY DIFFRACTION	2.71
5O0Y	TLK2 kinase domain from human	X-RAY DIFFRACTION	2.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UE8-F1	73.15	0.50

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Mental and behavioural disorders, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; nucleoli

Antibody reliability (HPA): IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
592	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
468–476	ATP
491	ATP

Post-translational modifications (7)

Type	Positions
Phosphoserine	73, 94, 99, 115, 117, 134, 750

Mutagenesis-validated functional residues (10)

Position	Phenotype
518	reduced kinase activity.
592	loss of kinase activity. no impact on interaction with asf1a.
613	loss of kinase activity.
617	increase in autophosphorylation.
617	loss of kinase activity.
659	reduced kinase activity.
686	reduced kinase activity.
695	reduced kinase activity.
720	reduced phosphorylation of asf1a.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 410 (showing top): WENDT_COHESIN_TARGETS_UP, RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_PEPTIDYL_SERINE_MODIFICATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AREB6_01, GOBP_CELLULAR_RESPONSE_TO_GAMMA_RADIATION, ATGCAGT_MIR217, CCATCCA_MIR432, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, AGGCACT_MIR5153P, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY

GO Biological Process (11): chromatin organization (GO:0006325), protein phosphorylation (GO:0006468), DNA damage response (GO:0006974), chromosome segregation (GO:0007059), negative regulation of autophagy (GO:0010507), peptidyl-serine phosphorylation (GO:0018105), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), intracellular signal transduction (GO:0035556), nucleus localization (GO:0051647), cellular response to gamma radiation (GO:0071480), regulation of chromatin organization (GO:1902275)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), intermediate filament (GO:0005882), perinuclear region of cytoplasm (GO:0048471), cytoskeleton (GO:0005856)

GO top-level categories

40 GO namespaces:

Category	Terms
protein kinase activity	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membraneless organelle	2
cellular component organization	1
phosphorylation	1
protein modification process	1
cellular response to stress	1
cell cycle process	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
protein phosphorylation	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
intracellular anatomical structure	1
signal transduction	1
organelle localization	1
response to gamma radiation	1
cellular response to ionizing radiation	1
chromatin organization	1
regulation of cellular component organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage response	BP	direct assay
cellular response to gamma radiation	BP	direct assay
chromosome segregation	BP	mutant phenotype
intracellular signal transduction	BP	direct assay
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	BP	mutant phenotype
nucleus localization	BP	mutant phenotype
peptidyl-serine phosphorylation	BP	direct assay
protein phosphorylation	BP	direct assay
regulation of chromatin organization	BP	direct assay
intermediate filament	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
ATP binding	MF	direct assay
identical protein binding	MF	physical interaction
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 1,676 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLK2	ASF1B	Q9NVP2	858
TLK2	ASF1A	Q9Y294	828
TLK2	SRSF1	Q07955	656
TLK2	AMMECR1L	Q6DCA0	615
TLK2	TMUB2	Q71RG4	611
TLK2	DDX50	Q9BQ39	594
TLK2	FCF1	Q9Y324	587
TLK2	DNAJC14	Q6Y2X3	559
TLK2	H1-0	P07305	551
TLK2	H3C1	P02295	522
TLK2	TBC1D10B	Q4KMP7	522
TLK2	H3-3A	P06351	519
TLK2	H3-4	Q16695	519
TLK2	H3-7	Q5TEC6	519
TLK2	H3-5	Q6NXT2	519
TLK2	H3C14	Q71DI3	519

IntAct

Human interaction partners of TLK2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

27 partners by confidence:

Partner	Interaction type	MIscore	Records
DYNLL1	association	0.890	4
ASF1A	phosphorylation reaction	0.740	1
CEP70	physical association	0.560	3
DMAP1	physical association	0.560	3
FRMD6	physical association	0.560	3
GMCL1	physical association	0.560	3
PAX5	physical association	0.560	3
PAX6	physical association	0.560	3
UBE2I	physical association	0.560	3
IRF4	physical association	0.500	1
IRF7	physical association	0.500	1
SMARCC2	physical association	0.500	1
H1-0	association	0.350	1
IGF2BP3	association	0.350	1
IGKV1D-13	association	0.350	1
PCNA	association	0.350	1
RPS27A	association	0.350	1
AQR	proximity	0.270	1
PES1	proximity	0.270	1
SBNO1	proximity	0.270	1
AMOTL1	physical association	0.000	1
ASF1B	physical association	0.000	1
CDADC1	physical association	0.000	1
COBLL1	physical association	0.000	1
DYNLL2	physical association	0.000	1
IFFO1	physical association	0.000	1
SCML1	physical association	0.000	1

BioGRID (220 interactions; top human partners by supporting records): TLK1 (Affinity Capture-MS; 11 records), ASF1A (Affinity Capture-MS; 9 records), ASF1B (Affinity Capture-MS; 9 records), DYNLL1 (Affinity Capture-MS; 6 records), DYNLL2 (Affinity Capture-MS; 4 records), CABIN1 (Affinity Capture-MS; 3 records), EID3 (Affinity Capture-MS; 3 records), LHX6 (Affinity Capture-MS; 3 records), RFPL3 (Affinity Capture-MS; 3 records), SMARCC2 (Affinity Capture-MS; 3 records), AURKA (Affinity Capture-Western; 2 records), CNTNAP1 (Affinity Capture-MS; 2 records), ELAVL2 (Affinity Capture-MS; 2 records), HIRA (Affinity Capture-MS; 2 records), IGF2BP1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
TLK2	“up-regulates quantity by stabilization”	ASF1A	phosphorylation
TLK2	unknown	ASF1B	phosphorylation
CHEK1	“down-regulates activity”	TLK2	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for TLK2: 321 ClinVar records (83 pathogenic / likely pathogenic); 1 CIViC cancer variant; 8 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

321 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	41
Uncertain significance	165
Likely benign	39
Benign	2

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 83 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
617919	NM_006852.6(TLK2):c.784C>T (p.Arg262Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
617928	NM_006852.6(TLK2):c.181C>T (p.Arg61Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
816982	NM_006852.6(TLK2):c.367C>T (p.Arg123Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
620238	NM_006852.6(TLK2):c.2089C>T (p.Arg697Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3337452	NM_006852.6(TLK2):c.839_840del (p.Gln280fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1320192	NM_006852.6(TLK2):c.31C>T (p.Arg11Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
617915	NM_006852.6(TLK2):c.1973C>G (p.Pro658Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1098360	NM_006852.6(TLK2):c.754C>T (p.Gln252Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1527973	NM_006852.6(TLK2):c.585C>A (p.Cys195Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
548935	NM_006852.6(TLK2):c.989C>A (p.Ser330Ter)	Pathogenic	criteria provided, single submitter	2
978814	NM_006852.6(TLK2):c.1357G>T (p.Glu453Ter)	Pathogenic	criteria provided, single submitter	2
3382792	NM_006852.6(TLK2):c.154-1G>A	Pathogenic	criteria provided, single submitter	2
521637	NM_006852.6(TLK2):c.1746del (p.Ala583fs)	Pathogenic	criteria provided, single submitter	1
617923	NM_006852.6(TLK2):c.202G>T (p.Glu68Ter)	Pathogenic	criteria provided, single submitter	1
617935	NM_006852.6(TLK2):c.37C>T (p.Gln13Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore TLK2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 1,959):

Position(s)	Effect	Δscore	Sites
17:62481119–62481120	acceptor_loss	1.0000	6
17:62481207	donor_loss	1.0000	2
17:62520771–62520772	acceptor_loss	1.0000	5
17:62520772	acceptor_gain	1.0000
17:62520845–62520846	donor_loss	1.0000	3
17:62522196	acceptor_gain	1.0000
17:62522202–62522203	acceptor_loss	1.0000	4
17:62522274	donor_gain	1.0000
17:62522274	donor_loss	1.0000
17:62523954	donor_gain	1.0000

AlphaMissense

2,902 missense substitutions predicted likely pathogenic (of 4,926 scored), across 578 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M631	9	0.952	0.999
M620	9	0.907	0.990
M290	9	0.896	0.990
H493	8	1.000	1.000
H510	8	1.000	1.000
D551	8	1.000	1.000
D592	8	1.000	1.000
N597	8	1.000	1.000
D613	8	1.000	1.000
F473	8	0.999	1.000
D481	8	0.999	1.000
H590	8	0.999	1.000
F649	8	0.999	1.000
D663	8	0.999	1.000
S474	8	0.998	1.000
F540	8	0.998	1.000
D553	8	0.998	1.000
F614	8	0.998	1.000
H437	8	0.997	1.000
H523	8	0.995	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	4.81e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	7.3e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000247

Disease associations

OMIM: gene MIM:608439 | disease phenotypes: MIM:618050, MIM:309800

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
intellectual disability, autosomal dominant 57	Definitive	Autosomal dominant	5

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Rare syndromic craniosynostosis or isolated multisuture synostosis	green
Fetal anomalies	amber

Mondo (4): intellectual disability, autosomal dominant 57 (MONDO:0054837), neurodevelopmental disorder (MONDO:0700092), syndromic microphthalmia (MONDO:0016073), intellectual disability (MONDO:0001071)

Orphanet (3): Syndromic microphthalmia-anophthalmia-coloboma (Orphanet:202948), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

53 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000358	Posteriorly rotated ears
HP:0000388	Otitis media
HP:0000426	Prominent nasal bridge
HP:0000455	Broad nasal tip
HP:0000486	Strabismus
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000545	Myopia
HP:0000581	Blepharophimosis
HP:0000582	Upslanted palpebral fissure
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000998	Hypertrichosis
HP:0001156	Brachydactyly
HP:0001195	Single umbilical artery
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001609	Hoarse voice
HP:0001763	Pes planus
HP:0002014	Diarrhea
HP:0002019	Constipation
HP:0002254	Intermittent diarrhea
HP:0002650	Scoliosis
HP:0002808	Kyphosis
HP:0002883	Hyperventilation
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0005780	Absent fourth finger distal interphalangeal crease
HP:0007018	Attention deficit hyperactivity disorder
HP:0009276	Contracture of the proximal interphalangeal joint of the 4th finger
HP:0011800	Midface retrusion
HP:0011968	Feeding difficulties
HP:0025161	Frequent temper tantrums
HP:0030051	Tip-toe gait
HP:0400000	Tall chin

GWAS associations

8 associations:

Study	Trait	p-value
GCST002846_1	Lifespan	5e-20
GCST90000025_539	Appendicular lean mass	3e-16
GCST006979_688	Heel bone mineral density	9e-14
GCST006979_689	Heel bone mineral density	5e-10
GCST90020028_1346	Hip circumference adjusted for BMI	1e-9
GCST90020028_1356	Hip circumference adjusted for BMI	1e-8
GCST90020025_287	Waist-to-hip ratio adjusted for BMI	2e-8
GCST90020027_1251	Waist-hip index	2e-8

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004980	appendicular lean mass
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5404 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 108,552 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

11 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL535	SUNITINIB	4	80,232
CHEMBL522892	DOVITINIB	3	5,162
CHEMBL300138	ENZASTAURIN	3	3,401
CHEMBL603469	LESTAURTINIB	3
CHEMBL475251	R-406	2	787
CHEMBL1721885	SU-014813	2	375
CHEMBL13608	TOCERANIB	2	1,225
CHEMBL1908397	KW-2449	1	655
CHEMBL258805	SU-9516	1	76

Clinical evidence (CIViC)

Drug × variant × indication, from 1 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

1 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
TLK2 Amplification	Go6983 + GF109203X	Breast Cancer	Sensitivity/Response	CIViC D	EID6000

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

Amplification.

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Tousled-like kinase (TLK) family

Binding affinities (BindingDB)

112 measured of 199 human assays (200 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
methyl N-[4-[5-[(2S)-2-amino-2,4-dimethylpentoxy]-6-chloro-2-pyridinyl]-2-pyridinyl]carbamate	IC50	0.5 nM	US-10155760: Biaryl kinase inhibitors
Staurosporine	KD	1.7 nM
CEP-701	KD	3.4 nM
DNDI1416941	IC50	4.2 nM
3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
Staurosporine, 8	IC50	6.5 nM
CHEMBL5549938	IC50	9.1 nM
CHEMBL5505789	IC50	12 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
CHEMBL5555013	IC50	15 nM
CHEMBL5505914	IC50	15 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
CHEMBL5555697	IC50	18 nM
CHEMBL5204542	IC50	19 nM
CHEMBL5556475	IC50	23 nM
CHEMBL5505934	IC50	26 nM
CHEMBL5556322	IC50	27 nM
CHEMBL5188455	IC50	33 nM
CHEMBL5523411	IC50	34 nM
CHEMBL5512470	IC50	36 nM
3-[(3-chlorophenyl)amino]-4-(2-methoxyphenyl)-2,5-dihydro-1H-pyrrole-2,5-dione	IC50	39 nM
CHEMBL5556177	IC50	46 nM
CHEMBL5559472	IC50	47 nM
CHEMBL5518017	IC50	48 nM
CHEMBL5558307	IC50	77 nM
CHEMBL5517951	IC50	88 nM
CHEMBL5555801	IC50	95 nM
CHEMBL5559206	IC50	100 nM
CHEMBL5555012	IC50	100 nM
CHEMBL5555855	IC50	100 nM
PKC-412	KD	110 nM
CHEMBL5556090	IC50	110 nM
CHEMBL5523653	IC50	110 nM
CHEMBL5555911	IC50	110 nM
CHEMBL5542185	IC50	120 nM
CHEMBL5505767	IC50	120 nM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	KD	120 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
CHEMBL5558654	IC50	130 nM
CHEMBL5517792	IC50	130 nM
CHEMBL5505761	IC50	140 nM
CHEMBL5518089	IC50	140 nM
CHEMBL5527885	KD	140 nM
CHEMBL235641	IC50	144 nM
CHEMBL5559521	IC50	150 nM
CHEMBL5523551	IC50	150 nM
CHEMBL5523586	IC50	160 nM
CHEMBL5173181	IC50	163 nM
CHEMBL5542171	IC50	170 nM

ChEMBL bioactivities

119 potent at pChembl≥5 of 119 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.57	IC50	2.71	nM	STAUROSPORINE
8.47	IC50	3.37	nM	STAUROSPORINE
8.44	IC50	3.66	nM	STAUROSPORINE
8.04	IC50	9.1	nM	CHEMBL5549938
7.92	IC50	12	nM	CHEMBL5505789
7.82	IC50	15	nM	CHEMBL5555013
7.82	IC50	15	nM	CHEMBL5505914
7.80	Kd	16	nM	STAUROSPORINE
7.75	IC50	18	nM	CHEMBL5555697
7.73	IC50	18.65	nM	CHEMBL5204542
7.64	IC50	23	nM	CHEMBL5556475
7.58	IC50	26	nM	CHEMBL5505934
7.57	IC50	27	nM	CHEMBL5556322
7.48	IC50	33.15	nM	CHEMBL5188455
7.47	IC50	34	nM	CHEMBL5523411
7.44	IC50	36	nM	CHEMBL5512470
7.34	IC50	46	nM	CHEMBL5556177
7.33	IC50	47	nM	CHEMBL5559472
7.32	IC50	48	nM	CHEMBL5518017
7.21	IC50	62	nM	CHEMBL107225
7.21	IC50	61	nM	CHEMBL235641
7.19	Kd	64	nM	LESTAURTINIB
7.17	IC50	67	nM	CHEMBL5542619
7.11	IC50	77	nM	CHEMBL5558307
7.06	IC50	88	nM	CHEMBL5517951
7.02	IC50	95	nM	CHEMBL5555801
7.01	IC50	97	nM	CHEMBL5555013
7.00	IC50	100	nM	CHEMBL5559206
7.00	IC50	100	nM	CHEMBL5555012
7.00	IC50	100	nM	CHEMBL5555855
6.96	IC50	110	nM	CHEMBL5556090
6.96	IC50	110	nM	CHEMBL5523653
6.96	IC50	110	nM	CHEMBL5555911
6.92	IC50	120	nM	CHEMBL5542185
6.92	IC50	120	nM	CHEMBL5505767
6.89	IC50	130	nM	CHEMBL5558654
6.89	IC50	130	nM	CHEMBL5517792
6.85	IC50	140	nM	CHEMBL5505761
6.85	IC50	140	nM	CHEMBL5518089
6.82	IC50	150	nM	CHEMBL5559521
6.82	IC50	150	nM	CHEMBL5523551
6.80	IC50	160	nM	CHEMBL5523586
6.79	IC50	163.4	nM	CHEMBL5173181
6.77	IC50	170	nM	CHEMBL5542171
6.75	IC50	180	nM	CHEMBL5556812
6.72	IC50	190	nM	CHEMBL5505927
6.72	IC50	190	nM	CHEMBL5542948
6.70	IC50	200	nM	CHEMBL5556132
6.66	IC50	220	nM	CHEMBL5556373
6.64	IC50	230	nM	CHEMBL5555777

PubChem BioAssay actives

119 with measured affinity, of 747 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	2198444: Inhibition of human TLK2 using casein as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assay	ic50	0.0027	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]-2-methoxybenzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0091	uM
4-cyano-N-[3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0120	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]thiophene-2-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0150	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]-1,3-oxazole-2-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0150	uM
N-[(3Z)-3-[(5-methyl-1H-imidazol-4-yl)methylidene]-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0180	uM
3-[(3E)-3-[2-(1-methylpyrrolidin-2-yl)ethoxyimino]indol-2-yl]-1H-indol-2-ol	1887963: Binding affinity to full length FLAG/HA/Strep-tagged TLK2 (388 to 772 residues) (unknown origin) transfected in HEK293T cells by Alexa Fluor 647 staining based FRET assay	ic50	0.0186	uM
N-(2-oxo-1,3-dihydroindol-5-yl)thieno[3,2-b]thiophene-5-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0230	uM
(3Z)-3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indole-5-carboxylic acid	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0260	uM
4-ethoxy-N-[3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]thiophene-2-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0270	uM
3-[(3E)-3-(1-methylpiperidin-4-yl)oxyiminoindol-2-yl]-1H-indol-2-ol	1887963: Binding affinity to full length FLAG/HA/Strep-tagged TLK2 (388 to 772 residues) (unknown origin) transfected in HEK293T cells by Alexa Fluor 647 staining based FRET assay	ic50	0.0331	uM
N-[3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0340	uM
N-[3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]thiophene-2-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0360	uM
N-[3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]-1,2-thiazole-5-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0460	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]thieno[3,2-b]thiophene-5-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0470	uM
3-cyano-N-[(3Z)-3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0480	uM
(8Z)-8-(1H-imidazol-5-ylmethylidene)-6H-pyrrolo[2,3-g][1,3]benzothiazol-7-one	2062923: Inhibition of TLK2 (unknown origin)	ic50	0.0610	uM
(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-1H-indole-5-carboxylic acid	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0620	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508112: Binding affinity to TLK2	kd	0.0640	uM
N-[(3Z)-3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]-2-methoxybenzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0670	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]-4-methoxythiophene-2-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0770	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]-4-methoxybenzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0880	uM
3-cyano-N-[3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.0950	uM
(3Z)-5-(furan-2-carbonyl)-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1000	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]cyclohexanecarboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1000	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]-3-methoxybenzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1000	uM
N-[(3Z)-3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1100	uM
N-[(3Z)-3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]-4-methoxybenzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1100	uM
2-fluoro-N-[(3Z)-3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1100	uM
N-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-5-yl]furan-2-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1200	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]-1,3-thiazole-2-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1200	uM
N-[(3Z)-3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]cyclohexanecarboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1300	uM
N-[(3Z)-3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]furan-2-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1300	uM
3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indole-5-carboxylic acid	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1400	uM
4-fluoro-N-[(3Z)-3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1400	uM
N-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-5-yl]cyclohexanecarboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1500	uM
(3Z)-5-acetyl-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1500	uM
(3Z)-3-(1H-imidazol-2-ylmethylidene)-5-propan-2-yloxy-1H-indol-2-one	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1600	uM
(3E)-3-[(3Z)-3-[2-(1-methylpiperidin-2-yl)ethoxyimino]-1H-inden-2-ylidene]-1H-indol-2-one	1887963: Binding affinity to full length FLAG/HA/Strep-tagged TLK2 (388 to 772 residues) (unknown origin) transfected in HEK293T cells by Alexa Fluor 647 staining based FRET assay	ic50	0.1634	uM
N-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-5-yl]butanamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1700	uM
4-fluoro-N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]thiophene-2-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1800	uM
4-fluoro-N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1900	uM
N-[3-(1H-imidazol-2-ylmethylidene)-2-oxo-1H-indol-5-yl]-2-(trifluoromethyl)benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.1900	uM
3-fluoro-N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]benzamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.2000	uM
(3Z)-5-butanoyl-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.2200	uM
(3Z)-5-butanoyl-3-(1H-imidazol-5-ylmethylidene)-1H-indol-2-one	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.2300	uM
(3Z)-3-(1H-imidazol-5-ylmethylidene)-5-methoxy-1H-indol-2-one	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.2400	uM
(3Z)-5-butanoyl-3-(1H-imidazol-2-ylmethylidene)-1H-indol-2-one	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.2500	uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]-1,3-benzodioxole-4-carboxamide	2062918: Inhibition of human TLK2 preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by hotspot assay	ic50	0.2600	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	436054: Binding constant for TLK2 kinase domain	kd	0.2700	uM

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	7
trichostatin A	affects cotreatment, decreases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Rotenone	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
nickel acetate	affects expression	1
K 7174	increases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	decreases expression	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
picoxystrobin	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	increases phosphorylation	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Antimycin A	decreases expression	1
Atrazine	decreases expression	1

ChEMBL screening assays

185 unique, capped per target: 185 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1059380	Binding	Inhibition of TLK2 assessed as enzyme activity at 1 uM relative to untreated control	Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00169611	Phase 4	COMPLETED	NF1-Attention: Study of Children With Neurofibromatosis Type 1 Treated by Methylphenidate
NCT03975829	Phase 4	ACTIVE_NOT_RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02471339	Phase 3	COMPLETED	Acceptance and Commitment Training for Adolescents and Young Adults With Neurofibromatosis Type 1, Plexiform Neurofibromas, and Chronic Pain
NCT03871257	Phase 3	ACTIVE_NOT_RECRUITING	A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
NCT04461886	Phase 3	TERMINATED	A Long-term Study of NPC-12G Gel in Neurofibromatosis Type I
NCT04924608	Phase 3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas
NCT05913037	Phase 3	ACTIVE_NOT_RECRUITING	FCN-159 in Adult Patients With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00021541	Phase 2	COMPLETED	R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
NCT00030264	Phase 2	COMPLETED	Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas
NCT00076102	Phase 2	COMPLETED	Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas
NCT00304083	Phase 2	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III or Stage IV Malignant Peripheral Nerve Sheath Tumors
NCT00326872	Phase 2	TERMINATED	AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine
NCT00589784	Phase 2	COMPLETED	Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT00634270	Phase 2	COMPLETED	A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis Type 1 Related Plexiform Neurofibromas
NCT00754780	Phase 2	COMPLETED	Clinical Trial of Pirfenidone in Adult Patients With Neurofibromatosis 1
NCT00846430	Phase 2	COMPLETED	Medical Treatment of High-Risk Neurofibromas
NCT00853580	Phase 2	COMPLETED	A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
NCT01125046	Phase 2	COMPLETED	Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas
NCT01402817	Phase 2	TERMINATED	Study of Sutent®/Sunitinib (SU11248) in Subjects With NF-1 Plexiform Neurofibromas
NCT01412892	Phase 2	COMPLETED	Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas
NCT01553149	Phase 2	COMPLETED	Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma
NCT01673009	Phase 2	COMPLETED	Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
NCT01968590	Phase 2	TERMINATED	Vitamin D Supplementation for Adults With Neurofibromatosis Type 1 (NF1)
NCT02096471	Phase 2	COMPLETED	MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1
NCT02101736	Phase 2	COMPLETED	Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults
NCT02332902	Phase 2	COMPLETED	Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T
NCT02407405	Phase 2	ACTIVE_NOT_RECRUITING	MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas
NCT02728388	Phase 2	TERMINATED	Photodynamic Therapy for Benign Dermal Neurofibromas- Phase II
NCT02839720	Phase 2	COMPLETED	Selumetinib in Treating Patients With Neurofibromatosis Type 1 and Cutaneous Neurofibroma
NCT02964884	Phase 2	ACTIVE_NOT_RECRUITING	Interventions for Reading Disabilities in NF1
NCT03090971	Phase 2	COMPLETED	Use of Topical Liquid Diclofenac Following Laser Microporation of Cutaneous Neurofibromas in Patients With NF1
NCT03109301	Phase 2	WITHDRAWN	Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in People With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST)
NCT03190915	Phase 2	ACTIVE_NOT_RECRUITING	Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
NCT03231306	Phase 2	COMPLETED	Phase II Study of Binimetinib in Children and Adults With NF1 Plexiform Neurofibromas
NCT03433183	Phase 2	COMPLETED	SARC031: MEK Inhibitor Selumetinib (AZD6244) in Combination With the mTOR Inhibitor Sirolimus for Patients With Malignant Peripheral Nerve Sheath Tumors
NCT03741101	Phase 2	UNKNOWN	Treatment of NF1-related Plexiform Neurofibroma With Trametinib
NCT03962543	Phase 2	ACTIVE_NOT_RECRUITING	MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas
NCT04435665	Phase 2	COMPLETED	NFX-179 Topical Gel Treatment in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF)
NCT04481035	Phase 2	COMPLETED	Antioxidant Therapy With N-acetylcysteine for Learning and Motor Behavior in Children With Neurofibromatosis Type 1
NCT04481048	Phase 2	COMPLETED	Antioxidant Therapy With N-acetylcysteine for Children With Neurofibromatosis Type 1
NCT05005845	Phase 2	COMPLETED	NFX-179 Topical Gel Treatment for Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF)
NCT05331105	Phase 2	RECRUITING	HL-085 in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas
NCT05735717	Phase 2	RECRUITING	MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies
NCT05825365	Phase 2	WITHDRAWN	Selumetinib in Chinese Paediatric With Post-operative NF1-PNs, PhaseⅡ, Double-Blinded, Placebo-Controlled Study
NCT06188741	Phase 2	RECRUITING	Selumetinib for the Prevention of Plexiform Neurofibroma Growth in NF Type 1
NCT06541847	Phase 2	RECRUITING	A Phase 2, Open-Label Study to Evaluate the Safety and Effects of HLX-1502 in Patients With Neurofibromatosis Type 1
NCT06620354	Phase 2	NOT_YET_RECRUITING	Clinical Study on the Treatment of Type I Neurofibromatosis With Smeitinib Hydrosulfate Capsule
NCT06621082	Phase 2	NOT_YET_RECRUITING	The Clinical Study of the Treatment of Patients With Type I Neurofibromatosis With Smetinib Hydrosulfate Capsule
NCT07521657	Phase 2	NOT_YET_RECRUITING	Efficacy of Mirdametinib Alone or Combination With Radiotherapy for Germline and Sporadic NF1-Altered High-Grade Glioma
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TLK2 across ~30M SureChEMBL compounds — explore on Sugi Predict.